This program project is a clinical research project with two auxiliary basic science components. The main goal of this program is to achieve a better understanding of the pathogenesis of neonatal germinal layer/intraventricular hemorrhage (GL/IVH) and the extent to which the severity of the disorder affects the central nervous system functions in both the immediate newborn period and in later life. Risk factors, both obstetric and neonatal, will be determined through combined effort in Projects 1 and 2. Also, a main component in Project 2 is taking into consideration the role of iatrogenic factors in the development of GL/IVH. Other components of Project 2 are physiologic clinical correlations and the early surgical intervention of post-hemorrhagic hydrocephalus. A sub-project in Project 2 is the development of a noninvasive intracranial pressure monitor. Whether GL/IVH may be related to prostaglandin metabolism, particularly with its prevention, will be studied in Project 3. In Project 4, the extent to which severity of GL/IVH contributes to long-term handicaps in premature babies will be evaluated. This project also will determine how outcome in GL/IVH may be affected by other variables such as birth weight, gestational age, Apgar scores, and many others studied in Projects 1 and 2. Project 5, with collaboration of Projects 2 and 3, will measure prostanoid levels in the spinal fluid of preterm infants with or without GL/IVH, with or without indomethacin therapy. Project 5 also will study the pharmacodynamics of the cerebral and umbilical vessels. Hypoxia or episodes of hypoxia/hyperoxia may be a common factor to both GL/IVH and retinopathy of prematurity (ROP). Clinical association between these two conditions has been reported. Project 6, in conjunction with Project 2, will attempt to investigate the common link between GL/IVH and ROP. It is hoped that this collaborative arrangement will lead to a better understanding of GL/IVH and would open new areas for future research, particularly in its prevention and treatment.